title: Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity.
abstract: OBJECTIVE
  This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers.
  
  
  METHODS
  A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P ≤ 0.05.
  
  
  RESULTS
  The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml(-1) h), (-)-ASOX by 358% (0.14 vs. 0.50 µg ml(-1) h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml(-1) h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml(-1) h).
  
  
  CONCLUSIONS
  The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Renata Monteiro
authors.initials: RM
authors.lastname: Lima
authors.forename: Maria Augusta Drago
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: de Jesus Ponte Carvalho
authors.forename: Bruno José
authors.initials: BJ
authors.lastname: Dumêt Fernandes
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Hector Hugo
authors.initials: HH
authors.lastname: Garcia
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000328:Adult; D015766:Albendazole / Q000097:blood / Q000493:pharmacokinetics*; D000977:Antiparasitic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D011223:Praziquantel / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D000977:Antiparasitic Agents; D011223:Praziquantel; D015766:Albendazole